Fig. 6

Schematic diagram of proposed mechanisms for glucose-regulated chondro-osteogenic differentiation via O-GlcNAcylation in CESCs. In degenerative disc disease, blood vessels grow into cartilage endplate and disturb the glucose environment. Elevated glucose produces more UDP-GlcNAc via the hexosamine biosynthesis pathway. Furthermore, the O-GlcNAcylation of Sox9 and Runx2 increases in CESCs with increased UDP-GlcNAc substrate. As a result, increasing O-GlcNAcylation modification of Sox9 inhibits Sox9 activity and chondrogenic differentiation, while increasing O-GlcNAcylation of Runx2 promotes Runx2 activity and osteogenic differentiation. Ultimately, the CEP shows decreased chondrogenesis and increased osteogenesis, which may aggravate degenerative disc disease